Effects of vasoactive cyclooxygenase products on shunt flow and extravascular lung water in acutely injured lungs

Using 50 mongrel dogs with alveolar flooding produced by oleic acid administration, the possible roles of vasoactive cyclooxygenase products on intrapulmonary shunt flow (Q̇(S)/Q̇(T)) and extravascular lung water (ETVI) in acutely injured lungs were assessed. Suppressing cyclooxygenase activity with indomethacin administration diminished the concentrations of thromboxane (TX) B₂ and 6-keto-prostaglandin F(1α) (6-keto-PGF(1α)) in arterial blood, resulting in a significant refuction in Q̇(S)/Q̇(T). Furthermore, indomethacin completely suppressed the increase in ETVI. Inhibition of TXA₂ generation by OKY-046 (thromboxane A₂ synthase blocker) diminished the concentration of TXB₂ while increasing that of 6-keto-PGF(1α) in blood. Administration of either OKY-046 or synthetic prostacyclin (PGI₂) markedly enhanced Q̇(S)/Q̇(T), in association with an increase in ETVI. In conclusion, the potent vasodilator prostacyclin was considered to enhance shunt flow, leading to the augmentation of edema formation.